Aggregated gold nanoparticles (AuNPs) in response to the acidic microenvironment of bacterial infection sites upon near-infrared (NIR) light irradiation provides a facile approach against bacterial infection. Generally, the aggregation of AuNPs with a larger size exhibit higher photothermal conversion efficiency. However, it remains challenging to construct pH-sensitive large-sized AuNPs due to their poor dispersive stability and insensitive stimuli-response. To address this challenge, zwitterionic peptide-modified AuNPs (AuNPs@ZP) with three different sizes (15, 40 and 60 nm) were fabricated to achieve the pH-induced aggregation and NIR photothermal antibacterial treatment. The self-complementary zwitterionic peptide (ZP) with the amino acid sequence of CVVVAAAEEEKKK was grafted on the surface of AuNPs, which underwent a fully reversible disassembly/aggregation switching process in response to pH changes. More importantly, AuNP40nm@ZP and AuNP60nm@ZP exhibited broadspectrum and efficient antibacterial activity upon 808 nm laser irradiation, due to their excellent photothermal conversion effect. This study provides a novel self-complementary zwitterionic peptide design to drive pH-induced large-sized AuNPs aggregate formation for better NIR photothermal antibacterial treatment.

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